The first specific aim of this project is to determine whether active immunization with a vaccine against cocaine will be medically safe and will develop sufficient antibody titers, during a 3-month induction period, to have potential clinical efficacy in humans. Three doses of the vaccine would be examined to test for a dose-related increase in antibody titer. As described in Project 1, the level of antibodies specific for the conjugate, for cocaine, and for the carrier protein, as well as the cocaine binding capacity, would be determined in samples of serum. The second specific aim is to follow up these subjects six and nine months after immunization to test for the persistence of the antibodies, as well as for relapse to cocaine abuse in subjects after leaving the residential treatment program. Following formal toxicological assessment of the acute and subacute outcomes associated with a vaccine against cocaine synthesized using the binding subunit of cholera toxin as a carrier, this project proposes administering this vaccine to humans who have used cocaine in the past and are currently in drug-free residential treatment for substance abuse. The goal is to assess whether sufficient antibody titers are generated to block modest doses of cocaine and to monitor adverse effects occurring during a 3-month period following vaccination. A residential setting would be used in an effort to insure that no cocaine use occurs during the antibody induction and to appropriately assess potential side effects due to antibody formation, without the confound of concurrent cocaine abuse. Moreover, since some adjustment of vaccine dose and the use of boosters may be needed to attain adequate antibody titers, this would be examined in the patients under scrutiny.